Document Detail

BAG3 directly interacts with mutated alphaB-crystallin to suppress its aggregation and toxicity.
MedLine Citation:
PMID:  21423662     Owner:  NLM     Status:  MEDLINE    
A homozygous disruption or genetic mutation of the bag3 gene causes progressive myofibrillar myopathy in mouse and human skeletal and cardiac muscle disorder while mutations in the small heat shock protein αB-crystallin gene (CRYAB) are reported to be responsible for myofibrillar myopathy. Here, we demonstrate that BAG3 directly binds to wild-type αB-crystallin and the αB-crystallin mutant R120G, via the intermediate domain of BAG3. Peptides that inhibit this interaction in an in vitro binding assay indicate that two conserved Ile-Pro-Val regions of BAG3 are involved in the interaction with αB-crystallin, which is similar to results showing BAG3 binding to HspB8 and HspB6. BAG3 overexpression increased αB-crystallin R120G solubility and inhibited its intracellular aggregation in HEK293 cells. BAG3 suppressed cell death induced by αB-crystallin R120G overexpression in differentiating C2C12 mouse myoblast cells. Our findings indicate a novel function for BAG3 in inhibiting protein aggregation caused by the genetic mutation of CRYAB responsible for human myofibrillar myopathy.
Akinori Hishiya; Mortada Najem Salman; Serena Carra; Harm H Kampinga; Shinichi Takayama
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-15
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-22     Completed Date:  2011-07-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e16828     Citation Subset:  IM    
Cardiovascular Group, Boston Biomedical Research Institute, Watertown, Massachusetts, United States of America.
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MeSH Terms
Adaptor Proteins, Signal Transducing / chemistry,  metabolism*
Amino Acid Sequence
Amino Acid Substitution / genetics
Cell Line
Molecular Sequence Data
Mutant Proteins / chemistry*,  toxicity*
Mutation / genetics
Protein Binding / drug effects
Protein Folding / drug effects
Protein Structure, Quaternary
Protein Structure, Tertiary
Solubility / drug effects
alpha-Crystallin B Chain / chemistry*,  toxicity*
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/BAG3 protein, human; 0/CRYAB protein, human; 0/Mutant Proteins; 0/alpha-Crystallin B Chain

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